Proline catalysis cycloaddition

Even though the use of (S)-proline (1) for the synthesis of the Wieland-Miescher ketone, a transformation now known as the Hajos-Parrish-Eder-Sauer-Wiechert reaetion, was reported in the early 1970s, aminocatalysis - namely the catalysis promoted by the use of chiral second-aiy amines - was rediscovered only thirty years later. The renaissance of aminocatalysis was prompted by two independent reports by List et al. on the asymmetric intermolecular aldol addition catalysed by (S)-proline (1) and by MacMillan et al. on the asymmetric Diels-Alder cycloaddition catalj ed by a phenylalanine-derived imidazolidinone 2. These two reactions represented the archetypical examples of asymmetric carbonyl compound activation, via enamine (Figure ll.lA) and iminium-ion (Figure 11.IB), respectively. 

Another example to illustrate the synthesis of proline derivatives 78 was published by Vicario and coworkers in 2013 [48]. Starting from aromatic aldehydes, diethyl malonate, and a,p-unsaturated aldehydes upon catalysis of unprotected diphenylprolinol, the synthesis of polysubstituted pyrrolidines was achieved in a one-pot condensation and [3+2] cycloaddition reaction in aqueous medium. 

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